[Research progress on C_(20)-diterpenoid alkaloids and their bioactivities in Ranunculaceae].

C_(20)-diterpenoid alkaloids are mainly distributed in plants of genus Aconitum, Delphinium, and Consolida in the Ranunculaceae. Their chemical structures are mainly categorized into nine types such as atisines, denudatines, hetidines, and hetisines. Bioactivity studies have shown that C_(20)-diterpenoid alkaloids have exhibited superior anti-tumor, analgesic, antiarrhythmic, and anti-inflammatory effects. In this review, the chemical structures and biological activities of 190 C_(20)-diterpenoid alkaloids reported in the Ranunculaceae from 2002 to the present were summarized, so as to provide a reference for the subsequent research on C_(20)-diterpenoid alkaloids in plants of Ranunculaceae.

[Construction of Saccharomyces cerevisiae cell factories for fermentation production of retinol].

Retinol is one of the main active forms of vitamin A, crucial for the organism's growth, development, and maintenance of eye and skin functions. It is widely used in cosmetics, pharmaceuticals, and feed additives. Although animals lack a complete pathway for synthesizing vitamin A internally, they can obtain vitamin A directly through diet or convert ß-carotene acquired from the diet. To boost the research on the biosynthesis of retinol, three different sources of alcohol dehydrogenase were firstly screened based on the ß-carotene synthesis platform CAR*1. It was determined that ybbO from Escherichia coli exhibited the highest catalytic activity,with a conversion rate of 95. 6%. To further enhance the reaction rate and yield of retinol, protein fusion technology was employed to merge two adjacent enzymes, blh and ybbO, within the retinol synthesis module. The evaluation was conducted using the high-yield engineered strain CAR*3 of ß-carotene. The optimal combination, blh-GGGS-ybbO, was obtained, with a 44. 9% increase in yield after fusion, reaching(111. 1± 3. 5) mg·L~(-1). Furthermore, through the introduction of human-derived retinol-binding protein(RBP4) and transthyretin(TTR), the process of hepatic cell secreting retinol was simulated in Saccharomyces cerevisiae, leading to an increased retinol yield of(158. 0±13. 1)mg·L~(-1). Finally, optimization strategies including overexpressing INO2 to enhance the reaction area for ß-carotene synthesis, enhancing hemoglobin VHb expression to improve oxygen supply, and strengthening PDR3m expression to facilitate retinol transport were implemented. A two-stage fermentation process resulted in the successful elevation of retinol production to(2 320. 0±26. 0)mg·L~(-1) in the fermentation tank of 5 L, which provided a significant foundation for the industrial development of retinol.

Insulating Material with Scale Components for High-Temperature and High-Pressure Water Applications.

Accurately measuring water holdup in horizontal wells is crucial for effectively using heavy oil reservoirs. The capacitance method is among the most widely used and accurate techniques. However, the absence of suitable insulating materials at high temperatures and pressures limits the effectiveness of capacitive water holdup measurement in heavy oil thermal recovery. This study introduces a new composite material based on an aviation-grade, special glass glaze as the insulating medium doped with inorganic components (CaSO4, MgSO4, Ca(OH)2, and SiO2). This new composite material demonstrates outstanding insulating performance under high-temperature and high-pressure conditions in water. A water environment with a high temperature of 350 °C and a pressure of 12 MPa considerably enhances the composite material's insulation. After 72 h of continuous use, the insulation performance remains 0.3 MΩ. The layers exhibit improved insulation and stability, maintaining integrity through five consecutive temperature shocks in 500 °C air and 20 °C water. XRD, IR, SEM, and TEM analyses reveal that the new composite material is amorphous after firing and that the addition of inorganic components improves the bonding between the glass glaze components and contributes to a denser structure. Simultaneously, SEM and TEM analyses indicate that adding inorganic components results in a smoother, crack-free, and more compact surface of the special glass glaze. This enhancement is crucial for the material's long-term stability in high-temperature and high-pressure water environments.

The value of SDC2 and Septin9 combined with serum tumor markers in early diagnosis of colorectal cancer.

OBJECTIVE: The aim of this study is to evaluate the significance of combined detection of Septin9 and syndecan-2 (SDC2) methylation markers and serum tumor markers for the early diagnosis of colorectal cancer. METHODS: A total of 116 patients diagnosed with colorectal cancer between December 2022 and February 2024 were designated as the colorectal cancer group. Additionally, 31 patients with colorectal adenoma were assigned to the adenoma group, while 44 individuals undergoing routine physical examinations were included in the control group. Concentrations of Septin9, SDC2, fecal occult blood (FOB), and four tumor markers-carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 724 (CA724)-were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves for Septin9, SDC2, the four tumor markers, FOB, the combination of Septin9 and SDC2, and the combined use of all seven indicators (CEA, CA19-9, CA125, CA72-4, FOB, Septin9, and SDC2). RESULTS: The colorectal cancer group exhibited the highest positive rates for Septin9, SDC2, the four tumor markers, the combined detection of Septin9 and SDC2, and the combined detection of all seven indicators, compared to both the adenoma and control groups (P < 0.05). The adenoma group also showed higher positive rates than the control group (P < 0.05). For patients with stage I-III colorectal cancer, the positive rates for the combined detection of Septin9 and SDC2 were 81.3%, 78.9%, and 90.2%, respectively, surpassing those for the combined detection of the four tumor markers (43.8%, 55.3%, and 61.0%). Additionally, the positive rates for the two-gene combination in stage III colorectal cancer were higher than those for FOB (P < 0.05). The sensitivity and area under the curve (AUC) for SDC2 were 73.3% and 0.855, respectively, exceeding the sensitivity and AUC for the combined four tumor markers, which were 60.3% and 0.734 (P < 0.05). The combined detection of the two methylated genes demonstrated a sensitivity of 86.2% and an AUC of 0.908, outperforming both FOB and the combined detection of the four tumor markers (P < 0.05). CONCLUSION: The detection of SDC2 exhibits high sensitivity for colorectal cancer, and when combined with Septin9, it significantly enhances the diagnostic accuracy for early-stage colorectal cancer, offering substantial clinical value.

A biomimetic targeted nanosystem delivering synergistic inhibitors for glioblastoma immune microenvironment reprogramming and treatment.

Efficient drug delivery across the blood-brain barrier is imperative for treating glioblastoma (GBM). This study utilized the GBM cell membrane to construct a biomimetic targeted nanosystem (GMNPs@AMD/RAPA) that hierarchically releases the CXCR4 antagonist AMD3100 and the mTOR pathway inhibitor rapamycin (RAPA) for reprogramming the tumor immune microenvironment and suppressing the progression of GBM. By initially inhibiting the CXCL12/CXCR4 axis, the tumor microenvironment (TME) was reprogrammed to enhance the infiltration of cytotoxic T lymphocytes (CTLs) into the TME while suppressing tumor cell survival, proliferation, and angiogenesis. Subsequently, through further cellular uptake and degradation of the nanoparticles, the mTOR pathway inhibitor RAPA was released, further suppressing the tumor progression. This study successfully combined chemotherapy and immunotherapy, achieving effective synergistic therapeutic effects, and suppressing the progression of GBM.

Aggregation-induced emission luminescence for angiography and atherosclerotic diagnosis.

Optical imaging technology has become increasingly recognized for its utility in diagnosing atherosclerosis thanks to advantages such as high spatial resolution, rapid data acquisition, lack of radiation exposure, cost-effectiveness, minimal invasiveness, and limited side effects. However, traditional luminogens employed in optical diagnostics are often troubled by aggregation-caused quenching (ACQ) effect, causing diagnostic errors in vivo. Since Professor Tang discovered the aggregation-induced emission (AIE) phenomenon, AIE luminogens (AIEgens) have been rapidly developing and are considered as the next-generation fluorescent contrast agents for angiography and atherosclerotic diagnosis. This mini review will outline the use of AIEgens in angiography and the diagnosis of atherosclerosis, exploring different imaging models, including second near-infrared, two/multi-photon, and photoacoustic imaging, and will provide a forward-looking perspective on their potential in atherosclerotic diagnosis.

Unusual polyunsaturated fatty acids in edible marine worms identified by covalent adduct chemical ionization mass spectrometry.

Non-traditional seafood, such as spoon worms (Urechis unicinctus) and peanut worms (Sipunculus nudus), serves as both delicacies and potential solutions to the global food insecurity crisis. Despite being consumed primarily in parts of China, Korea, and Japan, the nutritional values especially the complex fatty acid compositions of these marine worms are difficult to characterize. To overcome this obstacle, we employed covalent adduct chemical ionization (CACI) tandem mass spectrometry for the de novo identification of their unusual polyunsaturated fatty acids (PUFA). Through this method, we identified several PUFA with polymethylene-interrupted (PMI) double bond configurations, including 22:3(7Z,13Z,16Z), a novel PUFA derived from sciadonic acid. U. unicinctus exhibits an exceptionally low n-6/n-3 PUFA ratio of 0.15, making it a potential functional food to counterbalance the n-6/n-3 imbalance in modern diets. S. nudus boasts notably high concentrations (∼3 %, wt/wt) of branched chain fatty acids (BCFA), exceeding typical levels found in dairy products.

Appropriate flame-spraying treatment exacerbates thermal oxidative degradation of residual polyethylene films.

In dryland farming, plastic film mulching can significantly increase crop yields, but the resulting residues impair soil health. Heretofore, only few studies had examined how heat treatment facilitates the rapid degradation of polyethylene (PE) residual films. Herein, we characterized the variations in micro-morphology, functional groups, and crystallinity of PE residual films after moderate heat exposure using a self-made flame-spraying equipment. The results revealed that solid residues (SR) obtained from flame-spraying showed a gravimetric weight loss of 9.39 %-15.35 % compared with untreated PE residual films (UPF). Scanning electron microscope equipped with energy dispersive X-ray spectroscopy revealed considerable pits, cracks, and visible roughness in appearance and an increase in the oxygen-to­carbon (O/C) atomic ratio. Fourier-transform infrared spectroscopy identified characteristic oxygen-containing functional groups and double bonds. X-ray diffraction showed that flame-spraying treatments did not alter the crystal form of polymer, but increased the crystallinity. Higher flame-spraying temperatures resulted in larger oxygen-containing bond indices and lower crystallinity, suggesting a more severe decomposition of PE residual film. The possible volatile gaseous products at different reaction temperatures were predicted using thermogravimetric analysis coupled with Fourier transform infrared spectroscopy (TG-FTIR). Degradation of the PE residual film started at 220 °C, and concentrated release of major products such as long-chain aliphatic hydrocarbons, ketones, and CO2, occurred in the temperature range of 340 °C-440 °C. These results highlighted the effectiveness of the moderate flame-spraying method in accelerating rapid decomposition of residual films, and a flame-spraying temperature range of 220 °C-340 °C should be recommended to avoid potential environmental risks induced by the release of large quantities of degradation products. This study will contribute to enhance our understanding of the thermal oxidative degradation behavior of PE waste and provide a scientific basis for the rapid and clean establishment of PE residual films mitigation in agricultural fields.

Progression from cardiomyopathy to heart failure with reduced ejection fraction: A CORIN deficient course.

Cardiomyopathies, encompassing hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), constitute a diverse spectrum of heart muscle diseases that often culminating in heart failure (HF). The inherent molecular heterogeneity of these conditions has implications for prognosis and therapeutic strategies. Publicly available microarray and RNA sequencing (RNA-seq) data sets of HCM (n = 106 from GSE36961) and DCM (n = 18 from GSE135055 and 166 from GSE141910) patients were employed for our analysis. The Non-negative Matrix Factorization (NMF) algorithm was applied to explore the molecular stratification within HCM and DCM, and enrichment analysis was performed to delineate their biological characteristics. By integrating bulk and single-nucleus RNA-seq (snRNA-seq) data, we identified a potential biomarker for HCM progression and cardiac fibrosis, which was subsequently validated using mendelian randomization and in vitro. Our application of NMF identified two distinct molecular clusters. Particularly, a profibrotic, heart failure with reduced ejection fraction (HFrEF)-resembling Cluster 1 emerged, characterized by diminished expression of CORIN and a high degree of fibroblast activation. This cluster also exhibited lower left ventricular ejection fraction (LVEF) and worse prognostic outcomes, establishing the significance of this molecular subclassification. We further found that overexpression of CORIN could mitigate TGFß1-induced expression of col1a1 and α-SMA in neonatal rat cardiac fibroblasts. Our results indicated the heterogeneity of HCM population, and further evidenced the participation of corin in the progression of HCM, DCM and HFrEF. Nevertheless, our study is constrained by the lack of corresponding clinical data and experimental validation of the identified subtypes. Therefore, further studies are warranted to elucidate the downstream pathways of corin and to validate these findings in independent patient cohorts.

Thermoplastic PHB-Reinforced Chitosan Piezoelectric Films for Biodegradable Pressure Sensors.

Flexible and wearable pressure sensors have attracted significant attention in the fields of smart medicine and human health monitoring. Nevertheless, the design and fabrication of degradable disposable pressure sensors still face urgent challenges. Herein, we fabricated poly(3-hydroxybutyrate) (PHB)-reinforced chitosan (CS) piezoelectric films for intelligent sensors through a simple, low-cost, and environmentally friendly roll-forming method. The results show that PHB doping successfully increased the effective piezoelectric coefficient of the chitosan-based film from 40.12 to 49.38 pm/V (a 23% increase). Simultaneously, the pressure sensor based on the CS/PHB film exhibited excellent response sensitivity (484 mV/kPa) and a wide linear response range (0-130 kPa), which could be used as haptic sensors and motion monitoring sensors for the fast response to human motion signals. Additionally, the CS/PHB film could be completely degraded within 18 days in a natural soil environment, demonstrating outstanding degradability. Therefore, chitosan-based piezoelectric films with excellent biodegradability and piezoelectric characteristics have been successfully fabricated in this work, which will promote the innovative development of green chitosan-based electronic devices and disposable pressure sensors.

Expression patterns of housekeeping genes and tissue-specific genes in black goats across multiple tissues.

Black goats are a significant meat breed in southern China. To investigate the expression patterns and biological functions of genes in various tissues of black goats, we analyzed housekeeping genes (HKGs), tissue-specific genes (TSGs), and hub genes (HUBGs) across 23 tissues. Additionally, we analyzed HKGs in 13 tissues under different feeding conditions. We identified 2968 HKGs, including six important ones. Interestingly, HKGs in grazing black goats demonstrated higher and more stable expression levels. We discovered a total of 9912 TSGs, including 134 newly identified ones. The number of TSGs for mRNA and lncRNA were nearly equal, with 127 mRNA TSGs expressed solely in one tissue. Additionally, the predicted functions of tissue-specific long non-coding RNAs (lncRNAs) targeting mRNAs corresponded with the physiological functions of the tissues.Weighted gene co-expression network analysis (WGCNA) constructed 30 modules, where the dark grey module consists almost entirely of HKGs, and TSGs are located in modules most correlated with their respective tissues. Additionally, we identified 289 HUBGs, which are involved in regulating the physiological functions of their respective tissues. Overall, these identified HKGs, TSGs, and HUBGs provide a foundation for studying the molecular mechanisms affecting the genetic and biological processes of complex traits in black goats.

Clock protein LHY targets SNAT1 and negatively regulates the biosynthesis of melatonin in Hypericum perforatum.

Hypericum perforatum, also known as "natural fluoxetine," is a commonly used herbal remedy for treating depression. It is unclear whether melatonin in plants regulated by the endogenous circadian clock system is like in vertebrates. In this work, we found that the melatonin signal and melatonin biosynthesis gene, serotonin N-acetyltransferase HpSNAT1, oscillates in a 24-hour cycle in H. perforatum. First, we constructed a yeast complementary DNA library of H. perforatum and found a clock protein HpLHY that can directly bind to the HpSNAT1 promoter. Second, it was confirmed that HpLHY inhibits the expression of HpSNAT1 by targeting the Evening Element. Last, it indicated that HpLHY-overexpressing plants had reduced levels of melatonin in 12-hour light/12-hour dark cycle photoperiod, while loss-of-function mutants exhibited high levels, but this rhythm seems to disappear as well. The results revealed the regulatory role of LHY in melatonin biosynthesis, which may make an important contribution to the field of melatonin synthesis regulation.

As Aggregation-Induced Emission Meets with Noncovalent Conformational Locks: Subtly Regulating NIR-II Molecules for Multimodal Imaging-Navigated Synergistic Therapies.

Phototheranostics is growing into a sparking frontier in disease treatment. Developing single molecular species synchronously featured by powerful absorption capacity, superior second near-infrared (NIR-II) fluorescence and prominent photothermal conversion ability is highly desirable for phototheranostics, yet remains formidably challenging. In this work, we propose a molecular design philosophy that the integration of noncovalent conformational locks (NoCLs) with aggregation-induced emission (AIE) in a single formulation is able to boost multiple photophysical properties for efficient phototheranostics. The introduction of NoCLs skeleton with conformation-locking feature in the center of molecular architecture indeed elevates the structural planarity and rigidity, which simultaneously promotes the absorption capacity and bathochromic-shifts the emission wavelength centered in NIR-II region. Meanwhile, the AIE tendency mainly originated from flexibly propeller-like geometry at the ends of molecular architecture eventually endows the molecule with satisfactory emission intensity and photothermal conversion in aggregates. Consequently, by utilizing the optimized molecule, unprecedented performance on NIR-II fluorescence-photoacoustic-photothermal trimodal imaging-guided photothermal-chemo synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor ablation.

Structure of the endogenous insect acetyl-coA carboxylase carboxyltransferase domain.

Acetyl-coenzyme A carboxylases (ACCs) are pivotal in fatty acid metabolism, converting acetyl-CoA to malonyl-CoA. While ACCs in humans, plants, and microbes have been extensively studied, insect ACCs, crucial for lipid biosynthesis and physiological processes, remain relatively unexplored. Unlike mammals, which have ACC1 and ACC2 in different tissues, insects possess a single ACC gene, underscoring its unique role in their metabolism. Noctuid moths, such as Trichoplusia ni, are major agricultural pests causing significant crop damage and economic loss. Their resistance to both biological and synthetic insecticides complicates pest control. Recent research has introduced cyclic ketoenols as novel insecticides targeting ACCs, yet structural information to guide their design is limited. Here, we present a 3.12 Å cryo-EM structure of the carboxyltransferase (CT) domain of T. ni ACC, offering the first detailed structural insights into insect ACCs. Our structural comparisons with ACC CT domains from other species and analyses of drug binding sites can guide future drug modification and design. Notably, unique interactions between the CT and the central domain in T. ni ACC provide new directions for studying the ACC holoenzyme. These findings contribute valuable information for pest control and basic biological understanding of lipid biosynthesis.

The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.

Quercus dentata Thunb. leaves extract inhibits CaOx crystallization and ameliorates ethylene glycol-induced CaOx kidney stones via the OPN/CD44 and NLRP3 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus, with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones (Lin Zheng). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine. AIM OF STUDY: This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones. MATERIALS AND METHODS: The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD3 were compared in vivo. Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis. RESULTS: There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L-Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy (P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways. CONCLUSION: The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD.

Association between triglyceride glucose body mass index and urinary incontinence: a cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) 2001 to 2018.

BACKGROUND: Urinary incontinence (UI) is a prevalent, health-threatening condition that causes isolation and psychological strain, leading to significant personal distress. The connection between the triglyceride glucose body mass index (TyG-BMI) and UI remains elusive. The purpose of the current research was to investigate any possible relationships between raised TyG-BMI levels and a higher likelihood of UI. METHODS: For a thorough examination, adults 20 years and older with UI were included in cross-sectional research using the data obtained from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. Our investigation centred on three of the significant varieties of UI: Urgent Urinary Incontinence (UUI), Mixed Urinary Incontinence (MUI), and Stress Urinary Incontinence (SUI), employing weighted multivariate logistic regression models for an in-depth evaluation. The TyG-BMI, a possible biomarker, was arranged in increasing order among participants and then assessed with a trend test (P for trend). Moreover, this investigation delved into the non-linear relationships using advanced smoothed curve fitting techniques. Meticulous subgroup analyses were executed to verify the uniformity of the UI and TyG-BMI relationship across diverse demographic groups. RESULTS: A thorough investigation was conducted with 18,751 subjects to analyze the prevalence and types of UI, showing that 23.59% of individuals suffered from SUI, 19.42% from UUI, and 9.32% from MUI. Considering all possible confounding variables, Multivariate logistic regression analysis showed a substantial relationship between elevated TyG-BMI values and a greater likelihood across all UI categories. Specifically, stratifying the TyG-BMI into quartiles revealed a pronounced positive correlation in the top quartile relative to the bottom, reflected in increased odds ratios for SUI, UUI, and MUI (SUI: OR = 2.36, 95% CI 2.03-2.78, P < 0.0001; UUI: OR = 1.86, 95% CI 1.65-2.09, P < 0.0001; MUI: OR = 2.07, 95% CI 1.71-2.51, P < 0.0001). CONCLUSIONS: Among US adults, an association has been observed wherein increased TyG-BMI values correlate with a higher chance of UI. This suggests that TyG-BMI might be a helpful marker for identifying individuals at risk of UI, providing novel insights into its assessment and management.

Finite element model reveals the involvement of cartilage endplate in quasi-static biomechanics of intervertebral disc degeneration.

Background and objective: The intrinsic link between the compositional and structural attributes and the biomechanical functionality is evident in intervertebral discs. However, it remains unclear from a biomechanical perspective whether cartilage endplate (CEP) degeneration exacerbates intervertebral disc degeneration. Methods: This study developed and quantitatively validated four biphasic swelling-based finite element models. We then applied four quasi-static tests and simulated daily loading scenarios to examine the effects of CEP degradation. Results: Under free-swelling conditions, short-term responses were prevalent, with CEP performance changes not significantly impacting response proportionality. The creep test results showed the more than 50 % of the strain was attributed to long-term responses. Stress-relaxation testing indicated that all responses increased with disc degeneration, yet CEP degeneration's impact was minimal. Daily load analyses revealed that disc degeneration significantly reduces nucleus pulposus pressure and disc height, whereas CEP degeneration marginally increases nucleus pressure and slightly decreases disc height. Conclusions: Glycosaminoglycan content and CEP permeability are critical to the fluid-dependent viscoelastic response of intervertebral discs. Our findings suggest that CEP contributes to disc degeneration under daily loading conditions.

PEZy-miner: An artificial intelligence driven approach for the discovery of plastic-degrading enzyme candidates.

Plastic waste has caused a global environmental crisis. Biocatalytic depolymerization mediated by enzymes has emerged as an efficient and sustainable alternative for plastic treatment and recycling. However, it is challenging and time-consuming to discover novel plastic-degrading enzymes using conventional cultivation-based or omics methods. There is a growing interest in developing effective computational methods to identify new enzymes with desirable plastic degradation functionalities by exploring the ever-increasing databases of protein sequences. In this study, we designed an innovative machine learning-based framework, named PEZy-Miner, to mine for enzymes with high potential in degrading plastics of interest. Two datasets integrating information from experimentally verified enzymes and homologs with unknown plastic-degrading activity were created respectively, covering eleven types of plastic substrates. Protein language models and binary classification models were developed to predict enzymatic degradation of plastics along with confidence and uncertainty estimation. PEZy-Miner exhibited high prediction accuracy and stability when validated on experimentally verified enzymes. Furthermore, by masking the experimentally verified enzymes and blending them into homolog dataset, PEZy-Miner effectively concentrated the experimentally verified entries by 14∼30 times while shortlisting promising plastic-degrading enzyme candidates. We applied PEZy-Miner to 0.1 million putative sequences, out of which 27 new sequences were identified with high confidence. This study provided a new computational tool for mining and recommending promising new plastic-degrading enzymes.